Original Research ARTICLE
The Precise Diagnosis of Wolfram Syndrome Type 1 Based on Next-Generation Sequencing
- 1Shanghai Eye and ENT Hospital, Fudan University, China
- 2Key Laboratory of Visual impairment and Restoration, Eye & ENT Hospital, Fudan University, China
- 3Key Laboratory of Myopia, Ministry of Health, Fudan University, China
Purpose: To explore a method for the early, rapid and accurate diagnosis of Wolfram syndrome 1 (WS1) and further enrich the spectrum of WFS1 mutations in the Chinese population.
Methods: We analyzed 279 patients with unexplained optic atrophy using next-generation sequencing (NGS). All patients underwent detailed clinical evaluations. Furthermore, Sanger sequencing and cosegregation analyses were performed within families.
Results: Five patients with WS1 were identified in four unrelated families, and their clinical features were reviewed in detail. Seven variants of WFS1 were detected, including three reported variants (p.G674R, p.Tyr508Cysfs*34 and p.G702D) and four novel variants (p.W540G, p.K634*, p.F770C and p.Q584P). Furthermore, the variant p.G674R was recurrent.
Conclusion: Considering that WS1 is a rare progressive neurodegenerative disease, early diagnosis is beneficial to the systematic evaluation, monitoring and management of complications to improve patient quality of life and delay the progression of the disease. In the future, precise diagnosis on the basis of clinical manifestation and genetic testing will become the gold standard for the diagnosis of hereditary eye diseases and syndromes. Finally, our results further increase the spectrum of WFS1 mutations by adding four novel variants to the limited data available in the Chinese population.
Keywords: Wolfram Syndrome, WFS1, Optic Atrophy, Diabetes Mellitus, Next-generation sequencing, Precise diagnosis
Received: 31 Jan 2019;
Accepted: 04 Nov 2019.
Copyright: © 2019 Wang, Hu, Gao, Zhang, Xu, Tian and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Guohong Tian, Shanghai Eye and ENT Hospital, Fudan University, Shanghai, China, email@example.com
Dr. Jihong Wu, Shanghai Eye and ENT Hospital, Fudan University, Shanghai, China, firstname.lastname@example.org